By Turna Ray
Although Rules-Based Medicine is keeping a tight lid on its development and commercialization plans for diagnostic tests that will personalize Roche's schizophrenia treatments, the research and development pipelines at these companies may offer some hints.
The deal announced last week between Roche, RBM, and RBM's subsidiary Psynova Neurotech is an exclusive research and licensing agreement for the discovery, development, validation, and commercialization of diagnostic immunoassays that the partners are hoping to use for "differentiating" schizophrenia treatments.
Under the terms of the agreement, details of which were sparse, Roche will contract Psynova to identify candidate serum protein biomarkers for gauging disease progression and for predicting response to drugs in Roche's central nervous system pipeline. In order to discover these "biomarker signatures that could serve a companion diagnostic," Psynova will utilize its proprietary schizophrenia biomarker panels, its CNS disease database, as well as RBM’s DiscoveryMAP technology.
If a companion diagnostic results, it will be developed by Psynova, RBM, or independently by Roche. In the latter situation, Psynova would receive undisclosed milestone and royalty payments from Roche.
RBM would not discuss the timelines, scope, and financials associated with the agreement, citing competitive reasons and the early stage of the collaboration. "No firm determinations have been made regarding the viability of a companion diagnostic, so it's premature to discuss specifics or platforms," an RBM spokesperson told Pharmacogenomics Reporter in an e-mail last week. "Once validation work has been done on the drug development end utilizing the CNS biomarkers, the companies will evaluate whether/how to proceed with the companion diagnostic."
Roche's pipeline lists a glycine transporter-1 inhibitor (RG 1678) in Phase II development. In November, Roche reported results from a Phase II proof-of-concept study with the investigational compound, which showed that RG 1678 reduced negative symptoms and improved social functioning of schizophrenia patients. The 320-patient double-blind study showed that RG 1678 improved "negative or disorganized thought symptoms," and was well-tolerated at all tested doses. The findings were statistically significant.
Roche identifies "negative symptoms" of schizophrenia — a disease that affects 2 million people in the EU and 1.3 million in the US annually — as apathy, lack of pleasure, lack of emotion, and poor social functioning. These symptoms, researchers estimate, disable more than 50 percent of schizophrenia patients. "There are currently no effective therapies available for the treatment of negative symptoms," Roche said in a statement announcing the study results. Schizophrenia drugs that improve these "negative symptoms represent an important unmet medical need, and are associated with a substantial socio-economic burden," the company added.
RG 1678 is being co-developed globally with Japanese firm Chugai Pharmaceutical. Surely, further honing in on which patients' symptoms can be improved with the help of predictive and prognostic protein markers would allow Roche to capture a significantly sized market, as well as improve the clinical outcomes and costs associated with treatment. The World Health Organization estimates that schizophrenia affects as many as 24 million people worldwide and is most common in adults aged between 15 and 35 years.
Although RBM wasn't able to provide detailed information on a potential companion diagnostic or the biomarkers of interest, the company spokesperson noted that RBM and Psynova recently announced the discovery of a combination of protein biomarkers that have shown utility in "differential diagnosis of schizophrenia."
Psynova and RBM have been working for nearly two years on identifying CNS biomarkers. In October, Psynova and RBM announced results from a validation study retrospectively analyzing more than 1,100 blood samples from patients with central nervous system disorders such as schizophrenia, major depression, and bipolar disorder. Samples were also taken from age-matched controls.
"Obviously some of this research can be leveraged, which may have been part of the appeal for Roche," the RBM spokesperson said.
From this initial data, RBM and Psynova have developed a scoring algorithm based on significant biomarkers collected at a single site and then applied this algorithm to blinded samples collected at other sites. Using this algorithm in the study, researchers were able to distinguish schizophrenia patients from those with bipolar disorder, major depression, and normal controls.
"While several psychiatric conditions share symptoms, the clinical interventions vary, making it important to establish an accurate diagnosis as early as possible," Sabine Bahn, chief scientific officer of Psynova, said in a statement at the time. "We intend to develop a minimally invasive, objective test to aid the early diagnosis of schizophrenia and differentiation from bipolar disorder and major depression." RBM and Psynova plan to conduct studies to refine the predictive and prognostic utility of the biomarker panel in additional patients and in other CNS disorders.
As a result of this new clinical data, RBM in October made additional investments in Psynova and now holds controlling interest in the company.
The test for differentiating schizophrenia treatment will be first launched in RBM's CLIA laboratory, the company spokesperson said. Since the regulatory criteria for laboratory-developed tests is currently in flux at the US Food and Drug Administration, the RBM spokesperson held off on commenting whether a resulting companion test to a Roche drug will need to undergo FDA clearance or approval.
Although there may be leads in terms of tests and drug compounds in Roche and RBM/Psynova's pipeline, there is no indication at this time that RG 1678 will end up being paired with this specific biomarker panel.
"This alliance [with Roche] is part of an ongoing strategy to leverage the value of our biomarker portfolio in both the development of novel diagnostic aids for physicians and the accelerated development and delivery of novel therapeutics for patients," Psynova's Bahn said in a statement.
RBM is also making Rx/Dx deals a core part of its growth strategy, it seems.
In October, RBM launched CardiovascularMAP, a 50-biomarker panel combining biomarkers commonly associated with heart disease progression and markers linked to new patterns of disease, which the company is hoping will be a research tool for advancing drug development for heart disease at pharmaceutical and biotechnology companies.
Additionally, in November, RBM announced a deal with Covance, in which Covance will use RBM as its exclusive third-party provider of multiplexed protein biomarker testing services. In turn, RBM will use Covance exclusively as its referral laboratory testing service. The partnership is specifically aimed at fostering drug/diagnostic partnerships with pharma and biotech.